We have developed a breakthrough technology-The Somah Solution and Resuscitation System for the long-term preservation and prevention of ischemia- reperfusion injury of donor hearts upon transplant. Application of this technology upon successful completion of the proposed studies we believe, will create a new paradigm in heart transplant medicine. The Somah Solution allows for the successful harvesting of organs from non-beating heart donors one full hour post cessation of cardiocirculatory function, potentially negating the controversy associated with donation after cardiac death. The Resuscitation System allows for preservation, perfusion and resuscitation of the heart in a regenerative, self-sustaining system. Somah solution extracts atmospheric oxygen at physiological concentrations and facilitates synthesis of high-energy phosphates, even at hypothermic preservation, thus preventing cellular damage due to ischemia and energy depletion during storage. We have demonstrated the superiority of Somah over Celsior solution used in current practice by proving its ability to preserve non-beating and beating donor hearts in a fully viable state during conventional hypoxic and hypothermic storage. Unlike in other solutions, the hearts stored in Somah temporally recover mitochondrial and other biochemical functions during storage. Our groundwork demonstrates that non-beating donor porcine hearts are wholly preserved in a viable state for extended period post mortem. Preliminary functional studies show that hearts stored in Somah solution for 24 hours can be effectively resuscitated into normal sinus rhythm, without any pharmacological interventions, demonstrating fully efficient hemodynamic parameters. We will translate this technology to clinical application over the course of this grant by validating our observations in a porcine model of transplant, and in vitro, by preservation and resuscitation of donated human cadaveric hearts. This grant evaluates our hypotheses, that, Somah solution is a far superior substitute to current storage solutions for the procurement and preservation of beating and non-beating donor hearts, demonstrating a significant change in the modality of donation, storage and resuscitation. We will also demonstrate that Somah Solution and Perfusion system facilitates the harvesting of the non-beating donor hearts and their long-term preservation, resuscitation and transplantation. Successful translation of this technology will address the issues associated with organ donation, temporal and geographic constraints, making available hearts that are currently not used, and thus create an exemplar shift in the practice of transplant medicine and treatment of end stage heart failure. PUBLIC HEALTH RELEVANCE: The national VA statistics and epidemiological studies in the general population shows that our aging patient population is ravaged by CAD, congestive heart failure, and peripheral vascular disease leading to end stage heart failure. The only current treatment for end stage heart failure is transplant. Successful application of Somah will potentially facilitate supply-meeting demand; hence no Veteran that requires transplant will be left behind because of age and other factors. Therefore, we view these studies as directly relevant within the specific context of acute cardiovascular diseases characteristic of the VA's aging patient population. Additionally, this technology developed at the VA will help facilitate heart transplant the world over.